Conventional ampoules for containing a drug solution are mostly composed of glass. However, if a drug solution contained in such a glass ampoule has a higher pH, alkali flakes are liable to leach out of the ampoule. When the ampoule is opened, the ampoule is liable to cause injuries to one's fingers. Further, there are risks of fracture of the ampoule and contamination of the drug solution with shards of the ampoule produced when the ampoule is opened. The United States Food and Drug Administration (FDA) gives an advice against a risk that aluminum contained in the glass of the ampoule is liable to leach into the drug solution. In recent years, the glass ampoules have been replaced with plastic ampoules which are free from these risks.
Polyolefins such as polyethylene (PE) and polypropylene (PP) which are flexible and highly safe are typically used as a plastic material for the ampoule. The PE and the PP are highly stable against acidic drugs and alkaline drugs, but highly absorbent of and highly permeable to oxygen, air and carbon dioxide gas, etc. Therefore, the PE and the PP are not suitable as a material for an ampoule for containing an easily oxidizable drug or drug solution. Particularly, where the ampoule has a smaller volume, the content of the ampoule is reduced due to moisture permeation, thereby resulting in remarkable increase of the concentration of the drug in the drug solution.
Therefore, it is contemplated to use multilayer materials (laminate materials) imparted with gas and steam permeation preventing capabilities (barrier properties) as materials for film-formed products such as infusion bags and blow-molded products such as infusion bottles.
Plastic laminate materials are widely used for production of films and sheets. However, it is not appropriate to use such a film or a sheet for the production of the ampoule, so that the blow-molding method is inevitably employed for the production of the ampoule.
Ampoules produced by the blow-molding are disclosed in Japanese Patent Publication No. 2914826 and Japanese Unexamined Patent Publication No. SHO60 (1985)-24844. An ampoule (a sanitary product container) disclosed in the former publication is blow-molded from a polycycloolefin. An ampoule (a container for containing an injection drug) disclosed in the latter publication includes an air barrier layer of a material obtained by saponification of an ethylene-vinyl acetate copolymer (EVA) as an intermediate layer.
However, these publications merely teach that the ampoules are produced by the blow-molding. According to these publications, the sealing of each of the ampoules is achieved by heat-sealing an opening of the ampoule without formation of a seam after injecting a drug solution or charging a drug into the ampoule. In this case, the multilayer structure is liable to be broken by heat applied for the heat-sealing. As a result, the function and effect (the gas permeation preventing capability and the like) provided by employing the multilayer structure including the polycycloolefin or EVA layer are deteriorated.
Another production method for a drug solution filling plastic ampoule is a so-called blow-fill-seal process (see Japanese Examined Patent Publications No. SHO33 (1958)-8078 and No. SHO36 (1961)-5985, rommelag's Home Page “Welcome to Rommelag®” and “BFS Process—The Bottelpack® Process” retrieved from URL http://www.rommelag.com/ on Internet on Mar. 19, 2003).
The blow-fill-seal process includes the steps of forming an ampoule body by holding a tubular molten plastic parison by a main mold, filling a drug solution in the ampoule body, forming a head of an ampoule by a head mold, and sealing the ampoule, which are sequentially performed. Since the ampoule forming step, the drug solution filling step and the ampoule sealing step are sequentially performed, the blow-fill-seal process significantly differs from a simple blow-molding process, and the filling of the drug solution can be achieved more aseptically. In addition, the blow-fill-seal process is advantageous in that mass production can be realized.
However, a known ampoule produced by the blow-fill-seal process is a single layer ampoule composed of a polyolefin such as PE or PP. Therefore, it has not been contemplated to produce the ampoule of the laminate structure by the blow-fill-seal method and to impart one of the layers of the laminate structure with gas, steam, light ray and drug permeation preventing capabilities (barrier properties) and a drug absorption/adsorption preventing capability (see Japanese Examined Patent Publications No. SHO33 (1958)-8078 and No. SHO36 (1961)-5985, the aforementioned rommelag's Home Page, Mutual's Home Page “Packaging equipment—Container forming and aseptic filling system” retrieved from URL http://www.mutual.co.jp on Internet on Mar. 19, 2003, and Nisshin Pharmaceutical's Home Page “Polyethylene bottle” retrieved from URL http://www.yg-nissin.co.jp/BFS.htm on Internet on Mar. 19, 2003).
Exemplary methods for imparting the gas, steam, light ray and drug permeation preventing capabilities (barrier properties) and the drug absorption/adsorption preventing capabilities are to store the ampoule in a bag having a gas permeation resistance and to cover the surface of the ampoule with a material having the light ray permeation preventing capability (light barrier property) or with an exterior package. However, these methods additionally require the storage bag and materials for the surface coverage, thereby complicating the production process and increasing the production costs.